The variability existing among isolates of Simian hemorrhagic fever (SHF) virus from naturally infected patas monkeys has been studied. Differences were found among isolates in type and severity of disease produced in patas monkeys, cell sensitivity to infection, antigenicity and levels of specific antibody induced. Based on these criteria, isolates have been grouped into 4 strains, 2 of which produce acute infection in patas monkeys (LVR, P-180) and the other persistent infections (P-248, P-741). The P-180 strain induced the most severe disease symptoms in patas monkeys, but infections were rarely fatal. Persistently infected patas monkeys were viremic over a period of years but showed no signs or symptoms of infecion. Although none of the 4 strains induced cross neutralizing antibodies, 3 of them (LVR, P-180 and P-741) were antigenically closely related as determined by ELISA. High titers of IgG antibody (31,250 or greater than) were induced in patas monkeys infected with acute strains of SHF virus, but antibody was barely detectable inpersistently infected animals (50 or less than). LVR lytically infected MA-104 cells, patas macrophages (MAC) and rhesus MAC. Only patas MAC and rhesus were lytically infected by the P-180 strain, but the persistent strains lytically infected only rhesus MAC. SHF virus had no serological relationship to members of the currently recognized togavirus genera: alpha-, falvi-, pesti-and rubiviruses and, therefore, we have proposed that it be classified as a new genus of togaviruses. In vitro translation studies using LVR strain SHF virus genomic RNA and rabbit reticulocyte lysates have yielded translation product containing 4 polypeptides (40K, 25K, 16K and 12K daltons). These molecular weights correlate with those of structural polypeptides of SHF virions. Immunoprecipitation studies using specific hyperimmune sera and monoclonal antibodies support this conclusion. Our preliminary data, therefore, suggest that virion structural proteins are translated from the complete SHF virus genome, further implying that SHF virus translation more closely resembles that of flaviviruses than alphaviruses.